title: PIDD4, a novel PIDD isoform without the LRR domain, can independently induce cell apoptosis in cytoplasm.
abstract: PIDD1 (P53-induced death domain) is a pro-apoptotic gene which can be induced by p53. So far, three alternative splicing products of human PIDD gene have been identified. Here we report a new splicing variant of this gene and named it PIDD4. The coding sequence of PIDD4 contains intron 3 and a 60 bp insert at the 5' of exon 3. Each insertion has an in-frame stop codon, which makes PIDD4 get translated from exon 5 then. Therefore, PIDD4 protein lacks the 32 KD N-terminal peptide, missing the LRR domain found in the other three isoforms. In this study, we have shown that the expression of PIDD4 is also regulated by p53, and as PIDD2, it is not expressed in heart either. Moreover, PIDD4 is the only isoform which is expressed in skeletal muscle. This isoform mainly localizes in the cytoplasm, and produces a relatively higher proportion of PIDD-CC fragment. Overexpression of PIDD4 independently promotes apoptosis.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Dingding
authors.initials: D
authors.lastname: Han
authors.forename: Xianmei
authors.initials: X
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.forename: Guoqing
authors.initials: G
authors.lastname: Ji
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D020033:Protein Isoforms